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Objective: This study examines the veracity of self-reported data by applicants to psychiatry residency. Methods: The authors reviewed the reported publications of all applicants to a psychiatry residency training program over a 2-year span. Results: Nine percent of applicants reporting publications were found to have misrepresented them. International medical graduates were found to be more likely to have misrepresented their publications than U.S. medical graduates. Conclusion: A small but significant number of applicants to psychiatry residency training misrepresent their publications. Identification of misrepresentation may provide valuable information about the applicant and their future performance in training and practice.

Background: Major depressive disorder (MDD) is a global health concern. This study examined the efficacy, safety and tolerability of an extended-release (ER) formulation of levomilnacipran, an antidepressant approved for the treatment of MDD in adults. Methods: This 10-week (1-week placebo run-in period, 8-week double-blind treatment, 1-week down- taper), multicentre, double-blind, placebo- controlled, parallel-group, fixed-dose study was conducted between June 2011 and March 2012. Adult outpatients (age 18-75 yr) with MDD were randomly assigned (1:1:1) to placebo or to levomilnacipran ER 40 mg/day or 80 mg/day. For primary efficacy, we analyzed the Montgomery-Asberg Depression Rating Scale (MADRS) change from baseline to week 8 using a mixed-effects model for repeated-measures approach on the intent-to-treat (ITT) population. For secondary efficacy, we used the Sheehan Disability Scale (SDS), and for safety, we examined adverse events and laboratory, vital sign/physical and electrocardiography findings. Results: The ITT population consisted of 185 patients in the placebo group, 185 in the levomilnacipran ER 40 mg/day group and 187 in the levomilnacipran ER 80 mg/ day group. Study completion rates were similar among the groups (76%-83%). On MADRS change from baseline the least squares mean difference (LSMD) and 95% confidence interval (CI) versus placebo was significant for levomilnacipran ER 40 mg/day (- 3.3 [-5.5 to -1.1], p = 0.003) and 80 mg/day (-3.1, [-5.3 to -1.0], p = 0.004). On SDS change from baseline the LSMD (and 95% CI) versus placebo was also significant for levomilnacipran ER 40 mg/day (-1.8, 95% [-3.6 to 0], p = 0.046) and 80 mg/day (-2.7 [-4.5 to -0.9], p = 0.003). More patients in the levomilnacipran ER than the placebo group prematurely exited the study owing to adverse events; common adverse events (> 5% and > double the rate of placebo) were nausea, dry mouth, increased heart rate, constipation, dizziness, hyperhidrosis, urinary hesitation and erectile dysfunction. Limitations: Limitations to our study included short treatment duration and lack of an active control arm. Conclusion: Levomilnacipran ER at doses of 40 mg/day and 80 mg/day demonstrated efficacy on symptomatic and functional measures of MDD and was generally well tolerated in this patient population. Clinical trial registration: NCT01377194., Introduction Major depressive disorder (MDD) is a global health concern characterized by high lifetime prevalence and considerable disability. (1) The disorder typically has a recurrent course, with at least half [...]

Polysaccharides comprise an extremely important class of biopolymers that play critical roles in a wide range of biological processes, but the synthesis of these compounds is challenging because of their complex structures. We have developed a chemoenzymatic method for regioselective deprotection of monosaccharide substrates using engineered Bacillus megaterium cytochrome P450 ([P450.sub.BM3]) demethylases that provides a highly efficient means to access valuable intermediates, which can be converted to a wide range of substituted monosaccharides and polysaccharides. Demethylases displaying high levels of regioselectivity toward a number of protected monosaccharides were identified using a combination of protein and substrate engineering, suggesting that this approach ultimately could be used in the synthesis of a wide range of substituted mono- and polysaccharides for studies in chemistry, biology, and medicine. biocatalysis | demethylation | evolution | P450 | polysaccharide

Research was conducted to examine the alkylation of nucleic acids by a model quinone methide. A stable model compound, O-(tert-butyldimethylsilyl)-2-bromomethylphenol, was used to characterize the intrinsic reactivity of the species by generating an o-quinone methide in the presence of fluoride. Results indicate the ability of the exo-amine group of guanine to maintain its reactivity most effectively from nucleoside to helical DNA.

A parallel solution phase approach was applied in synthesizing a library of small molecules that recognize RNA. The core pyranoside containing the hydroxyamine core was modified at two locations through a combinatorial technique. A wide array of RNA binding affinities, which ranges approximately two orders of magnitude, were obtained from the compounds. The results suggested that the 1,3-hydroxyamine motif is capable of supporting the design of high affinity RNA binders.

A quantitative DNAse I footprint titration was conducted to determine the equilibrium association constants of 16 triple helical complexes which vary at a single site within the purine motif. The specific local triple helices were determined by comparing the differences in free energy values. Sequences of A-AT were more stable than T-CG, T-GC, and T-TA; A-AT is more stable than A-CG, A-GC and A-TA; and, G-GC were more stable than G-AT, G-TA and G-CG. T-CG was always more stable than bases opposite CG.